Both, the expression of HLA-G (a non-classical HLA class I molecule) and the loss of classical HLA class I molecules enable tumor cells to evade from immunosurveillance of the host. Whereas HLA-G down-modulates the immune functions of all cells participating in the immune defence mechanisms, defects on HLA class I expression result in the resistance of tumor cells to cytotoxic T lymphocytes attacks. This contribution reviews the HLA-G expression pattern in malignant melanoma lesions, its correlation to the loss of classical HLA class I antigens, and new aspects of HLA-G regulation.